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Thermoreversible poly(ethylene glycol)-g-chitosan hydrogel as a therapeutic T lymphocyte depot for localized glioblastoma immunotherapy.

Tsao CT, Kievit FM, Ravanpay A, Erickson AE, Jensen MC, Ellenbogen RG, Zhang M - Biomacromolecules (2014)

Bottom Line: Local immunotherapy has the potential to eradicate the residual infiltrative component of these tumors.Nuclear magnetic resonance spectroscopy confirmed the chemical structure of poly(ethylene glycol)-g-chitosan, and rheological studies revealed that the sol-to-gel transition of the PCgel occurred around ≥32 °C.Our study suggests that this unique PCgel depot may offer a viable approach for localized immunotherapy for glioblastoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.

ABSTRACT
The outcome for glioblastoma patients remains dismal for its invariably recrudesces within 2 cm of the resection cavity. Local immunotherapy has the potential to eradicate the residual infiltrative component of these tumors. Here, we report the development of a biodegradable hydrogel containing therapeutic T lymphocytes for localized delivery to glioblastoma cells for brain tumor immunotherapy. Thermoreversible poly(ethylene glycol)-g-chitosan hydrogels (PCgels) were optimized for steady T lymphocyte release. Nuclear magnetic resonance spectroscopy confirmed the chemical structure of poly(ethylene glycol)-g-chitosan, and rheological studies revealed that the sol-to-gel transition of the PCgel occurred around ≥32 °C. T lymphocyte invasion through the PCgel and subsequent cytotoxicity to glioblastoma were assessed in vitro. The PCgel was shown to be cellular compatible with T lymphocytes, and the T lymphocytes retain their anti-glioblastoma activity after being encapsulated in the PCgel. T lymphocytes in the PCgel were shown to be more effective in killing glioblastoma than those in the Matrigel control. This may be attributed to the optimal pore size of the PCgel allowing better invasion of T lymphocytes. Our study suggests that this unique PCgel depot may offer a viable approach for localized immunotherapy for glioblastoma.

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Related in: MedlinePlus

Chemistry of PEG-g-chitosan. (a) Chemicalstructureof PEG-g-chitosan. PEG is framed by the small dashedrectangle and chitosan by the large dashed rectangle. (b) NMR analysisof PEG-g-chitosan (purple) and pure chitosan (black).HOD is the abbreviation for deuterium oxide.
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fig1: Chemistry of PEG-g-chitosan. (a) Chemicalstructureof PEG-g-chitosan. PEG is framed by the small dashedrectangle and chitosan by the large dashed rectangle. (b) NMR analysisof PEG-g-chitosan (purple) and pure chitosan (black).HOD is the abbreviation for deuterium oxide.

Mentions: Panels a andb of Figure 1 show the chemical structure ofPEG-g-chitosan and the 1H NMR spectraof PEG-g-chitosan and pure chitosan, respectively.The characteristic signals of PEG-g-chitosan wereas follows: δ 4.9–5.0 (H-1), 3.6–4.3 (H-3, H-4,H-5, H-6, H-8, H-9, and H-10), 3.4 (H-11), 3.1–3.3 (H-2), and2.1 ppm (H-7). The characteristic signals of pure chitosan were asfollows: δ 5.0–5.2 (H-1), 3.7–4.2 (H-3, H-4, H-5,and H-6), 3.3–3.5 (H-2), and 2.25 ppm (H-7).20,21 Compared to those of pure chitosan, the peaks of PEG-g-chitosan in the range of 3.6–3.9 ppm were not well separated,because of the overlap of the more intense peak of the PEG methylenegroups with those of the saccharide backbone of chitosan. Furthermore,the methyl group of PEG in PEG-g-chitosan was seenclearly at 3.4 ppm.26 The observed changesin NMR analysis confirmed the successful grafting of PEG onto chitosan,and the grafted PEG in PEG-g-chitosan was determinedto be 60 wt %.


Thermoreversible poly(ethylene glycol)-g-chitosan hydrogel as a therapeutic T lymphocyte depot for localized glioblastoma immunotherapy.

Tsao CT, Kievit FM, Ravanpay A, Erickson AE, Jensen MC, Ellenbogen RG, Zhang M - Biomacromolecules (2014)

Chemistry of PEG-g-chitosan. (a) Chemicalstructureof PEG-g-chitosan. PEG is framed by the small dashedrectangle and chitosan by the large dashed rectangle. (b) NMR analysisof PEG-g-chitosan (purple) and pure chitosan (black).HOD is the abbreviation for deuterium oxide.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215871&req=5

fig1: Chemistry of PEG-g-chitosan. (a) Chemicalstructureof PEG-g-chitosan. PEG is framed by the small dashedrectangle and chitosan by the large dashed rectangle. (b) NMR analysisof PEG-g-chitosan (purple) and pure chitosan (black).HOD is the abbreviation for deuterium oxide.
Mentions: Panels a andb of Figure 1 show the chemical structure ofPEG-g-chitosan and the 1H NMR spectraof PEG-g-chitosan and pure chitosan, respectively.The characteristic signals of PEG-g-chitosan wereas follows: δ 4.9–5.0 (H-1), 3.6–4.3 (H-3, H-4,H-5, H-6, H-8, H-9, and H-10), 3.4 (H-11), 3.1–3.3 (H-2), and2.1 ppm (H-7). The characteristic signals of pure chitosan were asfollows: δ 5.0–5.2 (H-1), 3.7–4.2 (H-3, H-4, H-5,and H-6), 3.3–3.5 (H-2), and 2.25 ppm (H-7).20,21 Compared to those of pure chitosan, the peaks of PEG-g-chitosan in the range of 3.6–3.9 ppm were not well separated,because of the overlap of the more intense peak of the PEG methylenegroups with those of the saccharide backbone of chitosan. Furthermore,the methyl group of PEG in PEG-g-chitosan was seenclearly at 3.4 ppm.26 The observed changesin NMR analysis confirmed the successful grafting of PEG onto chitosan,and the grafted PEG in PEG-g-chitosan was determinedto be 60 wt %.

Bottom Line: Local immunotherapy has the potential to eradicate the residual infiltrative component of these tumors.Nuclear magnetic resonance spectroscopy confirmed the chemical structure of poly(ethylene glycol)-g-chitosan, and rheological studies revealed that the sol-to-gel transition of the PCgel occurred around ≥32 °C.Our study suggests that this unique PCgel depot may offer a viable approach for localized immunotherapy for glioblastoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.

ABSTRACT
The outcome for glioblastoma patients remains dismal for its invariably recrudesces within 2 cm of the resection cavity. Local immunotherapy has the potential to eradicate the residual infiltrative component of these tumors. Here, we report the development of a biodegradable hydrogel containing therapeutic T lymphocytes for localized delivery to glioblastoma cells for brain tumor immunotherapy. Thermoreversible poly(ethylene glycol)-g-chitosan hydrogels (PCgels) were optimized for steady T lymphocyte release. Nuclear magnetic resonance spectroscopy confirmed the chemical structure of poly(ethylene glycol)-g-chitosan, and rheological studies revealed that the sol-to-gel transition of the PCgel occurred around ≥32 °C. T lymphocyte invasion through the PCgel and subsequent cytotoxicity to glioblastoma were assessed in vitro. The PCgel was shown to be cellular compatible with T lymphocytes, and the T lymphocytes retain their anti-glioblastoma activity after being encapsulated in the PCgel. T lymphocytes in the PCgel were shown to be more effective in killing glioblastoma than those in the Matrigel control. This may be attributed to the optimal pore size of the PCgel allowing better invasion of T lymphocytes. Our study suggests that this unique PCgel depot may offer a viable approach for localized immunotherapy for glioblastoma.

Show MeSH
Related in: MedlinePlus